The O's, looking to win their first four league games of the season for the first time in their history, looked dead and buried following a disastrous opening 20 minutes.
Northampton Town started with a bang as the Cobblers, without a league win this season, raced into a two-goal lead after corners from Daniel Jones were turned in by Poul Hubertz and Chris Doig.
Northampton could not have scripted a better start and after Jones fired wide early on they took a deserved lead on 15 minutes.
The impressive Jones whipped in a corner from the left and Hubertz reacted first to send a looping header past Stuart Nelson.
Orient almost levelled when Wayne Gray's run took him clear of the visiting defence, but Adam Boyd just failed to touch home his cross.
But the rampant visitors grabbed a second goal on 20 minutes when Jones played in a corner, this time from the right, and an unmarked Doig fired home from 12 yards.
Orient finally settled and should have cut the deficit before the break. Both Boyd and Gray went clean through with just Mark Bunn to beat, but on each occasions the goalkeeper saved well.
Then on the stroke of half-time Chambers hit a post with a shot from the edge of the area.
But Orient came storming back in the second half and cut the deficit on 52 minutes when substitute Jason Demetriou 's shot was parried by Bunn and Chambers followed up to lash the rebound home.
Five minutes later Orient were level when Mkandawire fired home after the visitors failed to clear their lines.
Orient look set to complete a remarkable win as Paul Terry and Boyd, with two golden chances, went close, but a draw was just about the right result.